Omega-oxidation of monocarboxylic acids in rat brain.
The accumulation of dicarboxylic acids is a prominent feature of inborn and toxin induced disorders of fatty acid metabolism which are characterized by impaired mental status. The formation of dicarboxylic acids is also a critical step in liver in the induction of intracellular fatty acid binding proteins and the proliferation of peroxisomes. In order to understand what potential roles dicarboxylic acids have in brain, we examined the extent of omega-oxidation in rat brain. Homogenates of rat brain catalyze the omega-oxidation of monocarboxylic acids with a specific activity of between 0.87 and 5.23 nmol/mg of post-mitochondrial protein/h, depending on the substrate. The activity is remarkably high, between one-fourth and 4 times the activity found in rat liver, depending on the chain length of the substrate. Specific activity increases with increasing chain length of the substrate. The omega-oxidation of palmitic acid is linear over a range of 0.125-3.0 mg of protein and 5-50 microM substrate for up to 45 minutes of incubation. The product of omega-oxidation in brain is almost exclusively dicarboxylic acid. Cultured rat neurons, astrocytes, and oligodendrocytes all contain omega-oxidation activity. Western blots of rat brain homogenate demonstrate a protein that is recognized by antibody to rat liver CYP4A omega-hydroxylase. These results demonstrate that the omega-oxidative pathway is prominent in brain and could play a role in brain fatty acid metabolism.
Alexander
J J
JJ
University of Chicago Pritzker School of Medicine, Department of Pediatrics, The Joseph P. Kennedy Mental Retardation Center, IL 60637, USA.
Snyder
A
A
Tonsgard
J H
JH
D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000378:metabolism; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005232:Fatty Acids, Volatile / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009928:Organ Specificity; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity
D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D005232:Fatty Acids, Volatile; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A